rs7868111

Positions:

• chr9-134825764-T-C
• chr9-134825764-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000371817.8(COL5A1):​c.4955-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,488,796 control chromosomes in the GnomAD database, including 374,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38841 hom., cov: 33)
  • Exomes 𝑓: 0.71 (335731 hom.)
• Consequence: COL5A1 ENST00000371817.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.28

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

LOC101448202 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-134825764-T-C is Benign according to our data. Variant chr9-134825764-T-C is described in ClinVar as [Benign]. Clinvar id is 255092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.4955-28T>C		intron_variant		ENST00000371817.8	NP_000084.3
LOC101448202	NR_103451.2	n.71-5555A>G		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.4955-28T>C		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.4955-28T>C		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.4955-28T>C		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.4955-28T>C		intron_variant		2		ENSP00000360885	A2
COL5A1	ENST00000460264.5	n.423-28T>C		intron_variant, non_coding_transcript_variant		3
COL5A1	ENST00000465877.1	n.135-28T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108617 AN: 152074 Hom.: 38816 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.710

GnomAD3 exomes AF: 0.720 AC: 179176 AN: 248800 Hom.: 64616 AF XY: 0.726 AC XY: 97720 AN XY: 134560

Gnomad AFR exome AF: 0.731

Gnomad AMR exome AF: 0.661

Gnomad ASJ exome AF: 0.780

Gnomad EAS exome AF: 0.778

Gnomad SAS exome AF: 0.793

Gnomad FIN exome AF: 0.721

Gnomad NFE exome AF: 0.703

Gnomad OTH exome AF: 0.712

GnomAD4 exome AF: 0.708 AC: 945974 AN: 1336604 Hom.: 335731 Cov.: 18 AF XY: 0.710 AC XY: 477090 AN XY: 671614

Gnomad4 AFR exome AF: 0.736

Gnomad4 AMR exome AF: 0.665

Gnomad4 ASJ exome AF: 0.785

Gnomad4 EAS exome AF: 0.732

Gnomad4 SAS exome AF: 0.790

Gnomad4 FIN exome AF: 0.719

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.714 AC: 108690 AN: 152192 Hom.: 38841 Cov.: 33 AF XY: 0.718 AC XY: 53389 AN XY: 74400

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.709

Alfa AF: 0.666 Hom.: 4084

Bravo AF: 0.715

Asia WGS AF: 0.786 AC: 2729 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Fibromuscular dysplasia, multifocal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7868111; hg19: chr9-137717610;